Enhancing the tropism of bacteria via genetically programmed biosensors

The tropism of engineered bacteria in vivo can be enhanced by genetic circuits, linked by AND-gate logic, that couple bacterial sensing and growth. Engineered bacteria for therapeutic applications would benefit from control mechanisms that confine the growth of the bacteria within specific tissues or regions in the body. Here we show that the tropism of engineered bacteria can be enhanced by coupling bacterial growth with genetic circuits that sense oxygen, pH or lactate through the control of the expression of essential genes. Bacteria that were engineered with pH or oxygen sensors showed preferential growth in physiologically relevant acidic or oxygen conditions, and reduced growth outside the permissive environments when orally delivered to mice. In syngeneic mice bearing subcutaneous tumours, bacteria engineered with both hypoxia and lactate biosensors coupled through an AND gate showed increased tumour specificity. The multiplexing of genetic circuits may be more broadly applicable for enhancing the localization of bacteria to specified niches.

Automated summary

The tropism of engineered bacteria in vivo can be enhanced by genetic circuits, linked by AND-gate logic, that couple bacterial sensing and growth. Engineered bacteria for therapeutic applications would benefit from control mechanisms that confine the growth of the bacteria within specific tissues or regions in the body. Multiplexing of genetic circuits may enhance the localization of bacteria to specified niches, providing increased specificity for therapeutic applications.